Given the multi-focal nature of prostate cancer, treatment of localized prostate cancer requires destruction of the entire gland. Radiation therapy and radical prostatectomy are effective treatment, but are associated with significant morbidity. In order to minimize the complications of therapy for prostate cancer, new less invasive alternative treatments for localized prostate cancer must be explored to destroy all viable prostatic tissue and tumor. Radiofrequency thermal ablation has been used clinically for treatment of hepatic and other tumors throughout the body. However, this technique has not been fully investigated for the ablation of prostate tumors. A major challenge to clinical application of radiofrequency (RF) therapy is our inability to distinguish viable tissue/tumor from necrotic tissue during ablation. Lack of such definition may lead to over-treatment or under-treatment. Although ultrasound is used for guiding needle placement, conventional sonographic findings of gray scale and Doppler imaging cannot identify residual viable tissue/tumor. We propose to utilize ultrasound contrast agents to detect tumor microvasculature and parenchymal blood flow in the prostate. Based on the biological behavior of prostate cancer and our preliminary studies, we propose: (1) A new therapeutic strategy for the treatment of prostate cancer - RF ablation of the whole prostate, (2) A unique imaging modality for monitoring ablation of the prostate gland - contrast-enhanced sonography. The objective of the study is to optimize transrectal contrast-enhanced ultrasound for guidance and monitoring of whole prostate ablation for the treatment of prostate cancer. Contrast-enhanced sonographic imaging will facilitate detection of viable prostate tissue during RF ablation of the entire prostate gland. Contrast-enhanced imaging will allow us to use the minimum necessary energy to achieve a safe, minimally invasive ablation of prostate cancer. The specific aims of this project are (1) to use contrast-enhanced transrectal ultrasound (TRUS) to monitor and direct RF ablation of the entire prostate in an animal model, (2) to explore methods to protect the prostatic urethra and surrounding structures during RF therapy and (3) to establish RF parameters to optimize destruction of the prostate gland and simultaneously minimize damage to the surrounding tissues. Experiments will be performed in three sequential phases: (1) To establish the RF ablation parameters to ablate the entire prostate and to optimize procedures for contrastenhanced imaging to monitor RF ablation, (2) To establish cooling parameters to protect adjacent vital structures, (3) To test the effectiveness and consistency of contrast-enhanced TRUS to guide RF ablation of the entire prostate while eliminating damage to adjacent organs. Cross-sectional and volume data on ultrasound will be correlated with results on pathology. We will demonstrate that contrast-enhanced imaging of the prostate can optimize RF ablation of the prostate for future use in humans as an innovative treatment of prostate cancer.